普罗布考对动脉粥样硬化大鼠平滑肌细胞凋亡及p53和Fas蛋白表达的影响

目的探讨普罗布考防治动脉粥样硬化（AS）的机制。方法选用雄性大鼠,复制大鼠AS模型,随机分为动脉粥样硬化模型组、普罗布考组和正常对照组。大鼠造模成功后给予普罗布考治疗,6周后处死大鼠,采用流式细胞术检测平滑肌细胞凋亡率及凋亡相关基因p53和Fas蛋白的表达。结果模型组大鼠血管平滑肌细胞凋亡率明显高于对照组（P〈0．05）,p53和Fas蛋白的表达增强（P％0．05）,主动脉壁可肉眼观测典型斑块。普罗布考组大鼠平滑肌细胞的凋亡率明显低于模型组（P〈0．05）,p53和Fas蛋白表达下调（P〈0．05）,主动脉斑块面积较模型组减小明显。结论普罗布考通过调节p53和Fas蛋白表达来调节AS大鼠平滑肌细胞的凋亡。     

雷公藤甲素对病毒性心肌炎细胞凋亡及Fas/FasL 蛋白表达的研究

目的:研究雷公藤甲素对柯萨奇病毒B3病毒(CVB3)感染的病毒性心肌炎小鼠心肌细胞凋亡和Fas/FasL蛋白表达的抑制作用,探讨TP治疗病毒性心肌炎的作用机制。方法:将Balb/c小鼠随机分成4组作为动物模型,分别为对照组、模型组、利巴韦林组和TP组。对照组腹腔注射生理盐水,其余三组腹腔注射CVB3,利巴韦林组和TP组小鼠分别予以相应的药物治疗后,测定各组小鼠存活率及心肌病变积分,采用末端转移酶标记技术(TUNEL法)检测小鼠心肌细胞凋亡,免疫组化法检测Fas/FasL蛋白阳性表达。结果:空白对照组心肌无病变,利巴韦林组、TP组与模型组相比有显著性差异(P<0.01)。正常组鲜见心肌细胞凋亡,模型组细胞凋亡率较正常组显著增加(P<0.01),治疗组利巴韦林组和TP组凋亡率比模型组明显降低(P<0.05,P<0.01)。模型组Fas/FasL表达比正常组显著增多(P<0.01),治疗组利巴韦林组和TP组较模型组显著降低(P<0.01)。结论:雷公藤甲素具有通过抑制Fas/FasL蛋白的表达,减缓心肌细胞凋亡,达到抑制病毒性心肌炎从而保护心肌细胞的作用。     

姜黄素对慢性低O2高CO2作用下大鼠脑组织Fas/FasL表达的影响

目的：观察慢性低02高C02作用下大鼠脑组织Fas/FasL表达及神经细胞超微结构变化,探讨姜黄素是否能影响慢性低O2高CO2作用下Fas/FasL表达以及脑神经细胞的超微结构变化。方法：将健康sD雄性大鼠15只,随机分为常氧对照组、慢性低02高c02组、慢性低O2高CO2姜黄素组（姜黄素采用灌胃给药,150mg/（kg·d）;应用免疫组织化学法和蛋白免疫印记法对脑神经细胞凋亡分子Fas/FasL的表达进行定性、定量测定,透射电镜下观察大脑皮质神经细胞超微结构形态学改变。结果：①免疫组织化学和蛋白免疫印记法显示,慢性低O2高CO2组中脑组织Fas/FasL的表达显著高于常氧对照组和慢性低O2高CO2姜黄素组。②脑组织的透射电镜结果显示,常氧对照组神经细胞及细胞器结构形态正常;慢性低O2高CO2组可见神经细胞和细胞器肿胀,细胞核染色质边集,出现凋亡小体;慢性低O2高CO2姜黄素组神经细胞核、细胞器、血管的形态结构基本正常。结论：①慢性低O2高CO2可上调脑组织Fas/FasL的表达,并诱导脑神经细胞呈现凋亡的超微结构变化;②姜黄素可能通过抑制Fas/FasL的表达减轻慢性低O2高CO2诱导的脑神经细胞的超微结构变化。     

内耳免疫反应诱导Fas和FasL表达与凋亡的关系

目的研究内耳免疫反应过程中是否存在细胞凋亡,以及细胞凋亡是否与Fas和FasL信号转导有关.方法选用雌性白色豚鼠16只,随机分为实验组和对照组各8只,以钥孔虫戚血蓝蛋白(keyhole limpet hemocyanin,KLH)全身免疫后,实验组以相同抗原进行内耳免疫,对照组内耳注射等量的磷酸盐缓冲生理盐水(phosphate buffered saline,PBS),在内耳免疫5d后处死动物,取内耳免疫侧耳蜗做石蜡切片.通过脱氧核糖核苷酸末端转移酶介导的缺口末端标记技术(terminal-deoxynucleotidyl transferase mediated nick end labeling,TUNEL)检测内耳凋亡细胞,免疫组化检测内耳Fas和FasL的表达.结果实验组豚鼠内耳Corti器毛细胞,血管纹的缘细胞和螺旋神经节细胞存在TUNEL染色阳性细胞,而对照组动物切片仅在支持细胞、血管纹和螺旋神经节细胞中发现极少数TUNEL染色阳性细胞.免疫组化染色实验组Corti器、螺旋神经节细胞、血管纹和螺旋韧带Fas和FasL蛋白表达阳性,而对照组只有螺旋神经节细胞和血管纹有较弱的Fas蛋白表达,FasL蛋白表达阴性.结论内耳免疫反应可诱导细胞凋亡的发生,Fas-FasL途径是参与此过程重要的信号转导途径之一.     

夏枯草胶囊对自身免疫性甲状腺炎大鼠甲状腺组织及Fas、FasL表达的影响

目的:探讨夏枯草胶囊对自身免疫性甲状腺炎(AITD)大鼠甲状腺组织病理学及Fas、FasL表达的影响。方法:将40只雌性SD大鼠按照随机数表法随机分为空白对照组、模型组、夏枯草胶囊组、硒酵母组,每组10只,空白对照组予以正常饲养,模型组和药物组予以PTg皮下注射建立AITD模型,夏枯草胶囊组、硒酵母组分别给予夏枯草胶囊与硒酵母片的生理水溶液灌胃,药物干预6周后处死大鼠,取甲状腺组织,HE染色电镜下观察各组大鼠甲状腺组织形态,免疫组化法检测各组大鼠甲状腺组织Fas、FasL蛋白的表达。结果:1)模型组大鼠甲状腺组织滤泡大量破坏,形态不规则,胶质分布不均匀,滤泡间隙增大,可见大量淋巴细胞及浆细胞浸润。夏枯草胶囊组滤泡形态尚规则,胶质含量较空白组少,滤泡间有少量淋巴细胞浸润。与模型组对比,夏枯草胶囊组与硒酵母组滤泡破坏及淋巴细胞浸润有显著改善。2)对照组大鼠甲状腺组织中Fas、FasL蛋白仅呈少量表达,模型组大鼠甲状腺组织中Fas、FasL蛋白表达较对照组显著增加(P0.01),夏枯草胶囊组大鼠甲状腺组织中Fas、FasL蛋白表达较模型组及硒酵母组均显著减少(P0.01)。结论:夏枯草胶囊可能通过减少Fas、FasL的表达,抑制甲状腺滤泡细胞凋亡,从而减轻甲状腺滤泡上皮的破坏。     

槲皮素对乳腺癌MCF-7和MDA-MB-435细胞的凋亡作用及机制研究

摘要 目的：探讨槲皮素对乳腺癌MCF-7和MDA-MB-435细胞的凋亡作用,并探讨其作用机制。方法：采用活细胞计数法(CCK-8)测定槲皮素对乳腺癌MCF-7和MDA-MB-435细胞增殖的作用,分别采用细胞划痕实验和Transwell实验测定槲皮素对乳腺癌MCF-7和MDA-MB-435细胞迁移和侵袭的影响,采用流式细胞术测定槲皮素对乳腺癌MCF-7和MDA-MB-435细胞凋亡的作用,采用实时荧光定量聚合酶链反应(qRT-PCR)和免疫印迹法(West-blotting)测定槲皮素对乳腺癌MCF-7和MDA-MB-435细胞Fas、FasL、Bcl-2和Bax mRNA和蛋白表达的影响。结果：槲皮素（50~200 μmol/L）作用乳腺癌MCF-7和MDA-MB-435细胞 24 h、48 h和72 h对其增殖具有显著的抑制作用,并且呈浓度依赖性（P<0.05）;细胞划痕实验中槲皮素50 μmol/L和100 μmol/L可使乳腺癌MCF-7和MDA-MB-435细胞划痕宽度较对照组显著增加（P<0.05）;Transwell试验中槲皮素50 μmol/L和100 μmol/L可使乳腺癌MCF-7和MDA-MB-435穿膜细胞较对照组显著降低（P<0.05）;槲皮素50 μmol/L和100 μmol/L可使乳腺癌MCF-7和MDA-MB-435细胞凋亡率较对照组显著升高（P<0.05）;槲皮素50 μmol/L和100 μmol/L可使乳腺癌MCF-7和MDA-MB-435细胞中Bcl-2 mRNA表达较对照组显著降低（P<0.05）,Fas、FasL和Bax mRNA表达较对照组显著升高（P<0.05）;槲皮素50 μmol/L和100 μmol/L可使乳腺癌MCF-7和MDA-MB-435细胞中Bcl-2 蛋白表达较对照组显著降低（P<0.05）,Fas、FasL和Bax 蛋白表达较对照组显著升高（P<0.05）。结论：槲皮素可促进乳腺癌细胞的凋亡,可能与其通过作用Fas/FasL凋亡信号通路而激活外源性凋亡途径,通过作用Bcl-2凋亡信号通路而激活内源性凋亡途径有关。     

细胞凋亡及API5与糖尿病性勃起功能障碍的相关性研究

为探讨糖尿病(DM)大鼠阴茎海绵体凋亡情况,以及与API5表达的相关性,采用链脲佐菌素(STZ)诱导建立糖尿病大鼠模型,并使用APO阴茎勃起实验筛选DMED大鼠并检测各组大鼠阴茎海绵体压力(ICP).10周后取大鼠阴茎海绵体组织,通过原位末端标记法(TUNEL)和免疫组织化学法分别检测阴茎海绵体细胞凋亡及API5的表达情况.在该实验中,动物模型血糖浓度:观察组显著高于对照组(P<0.05);体重变化:观察组明显低于对照组(P<0.05);观察组ICP和ICP/MAP均明显低于对照组(P<0.05);观察组大鼠阴茎海绵体组织的细胞凋亡较对照组显著升高(P<0.05);观察组大鼠阴茎海绵体组织中API5蛋白表达较对照组明显减少.通过实验,可了解DM大鼠阴茎海绵体细胞凋亡率增加,这可能是糖尿病性勃起功能障碍的发病机制之一,而API5可能参与了DM大鼠阴茎海绵体细胞凋亡的基因调控.     

牙龈卟啉单胞菌感染通过激活NLRP3小体诱导牙周膜细胞炎症反应及凋亡效应

目的观察牙龈卟啉单胞菌感染通过激活含NLR家族PYRIN域蛋白3(NLRP3)小体诱导人牙周膜细胞(hPDLCs)炎症反应及凋亡的效应。方法取健康前磨牙样本并分离培养hPDLCs,分为牙龈卟啉单胞菌感染的感染组和常规处理的对照组,检测细胞中NLRP3小体[NLRP3、凋亡相关斑点样蛋白(ASC)、含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-1]、凋亡基因[自杀相关因子(Fas)、Fas配体(FasL)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关x蛋白(Bax)、Caspase-3]的表达量及培养基中炎症细胞因子[白细胞介素(IL)-1β、IL-18、肿瘤坏死因子-α(TNF-α)]的含量。结果感染组hPDLCs中NLRP3、ASC、Caspase-1、Fas、FasL、Bax、Caspase-3的表达量及培养基中IL-1β、IL-18、TNF-α的含量明显高于对照组,细胞中Bcl-2的表达量明显低于对照组。结论牙龈卟啉单胞菌感染能够诱导hPDLCs的炎症反应及凋亡且该作用与NLRP3小体的激活有关。     

唐古拉红景天防治肝纤维化机制研究

目的：探讨唐古拉红景天对肝纤维化的治疗作用,并探讨作用机制。方法：将60只wistar大鼠随机分为正常组、模型组和红景天治疗组。采用CCL4复合造模法造成肝纤维化,同时进行不同药物治疗,6周后采血并处死动物取材做病理学检查。采用免疫组化检测肝组织中Fas、FasL和NF-кB蛋白含量的表达,采用放射免疫法检测血清LN和FN的含量。结果：模型组肝小叶结构紊乱,出现脂肪变性及大量气球样变,中央静脉及汇管区周围胶原纤维组织明显增多。正常组和治疗组肝小叶结构规则。正常组肝组织Fas、FasL蛋白呈棕黄色弱阳性表达,模型组Fas、FasL蛋白较正常组明显增强（P〈0.05）;治疗组Fas、FasL蛋白的表达均较模型组有明显的减弱（P〈0.05）;正常组肝组织NF-κB蛋白呈棕黄色阳性强表达,模型组NF-κB蛋白的表达较正常组明显减弱（P〈0.05）;治疗组NF-κB蛋白的表达较模型组有明显的增强（P〈0.05）;模型组血清Ⅲ型前胶原氨基端肽（PⅢNP）、LN的表达较正常组明显增强（P〈0.05）;治疗组血清PⅢNP、LN的表达均较模型组有明显的减弱（P〈0.05）。结论：唐古拉红景天通过抑制肝细胞的凋亡对肝纤维化具有一定的防治作用。     

Bcl-2、Fas和FasL在BPH组织中的表达及其意义

目的:研究凋亡相关基因Bcl-2、Fas和FasL在前列腺增生组织中表达,并探讨其与前列腺增生症的关系.方法:收集哈尔滨医科大学附属第二医院2004年5月--2005年8月前列腺增生症(BPH)组织标本36例,前列腺癌(PCa)组织标本12例和正常前列腺(NP)组织标本7例.应用免疫组织化学SABC方法,检测BPH、PCa和NP组织标本中凋亡相关基因Bcl-2、Fas和FasL的表达,并探讨Bcl-2、Fas和FasL的表达与前列腺增生症的关系.结果:①BPH与PCa组Bcl-2蛋白阳性表达明显高于NP组(P<0.05),而BPH组与PCa组阳性表达无显著差异;PCa组Fas表达显著低于BPH和NP(P<0.05、0.01),而BPH和NP组之间差异也有显著性(P<0.05);FasL在三组之间表达差异均无显著性(P>0.05).②在BPH组织中Bcl-2的表达与Fas表达呈负相关(P(0.05),与FasL表达呈正相关(P<0.05),余均未见相关性.结论:Bcl-2、Fas、FasL均参与了BPH的发生发展过程,Bcl-2、Fas、FasL表达的综合结果可能是引起BPH的原因之一.     

在HBV感染的肝癌组织中Fas/FasL表达的作用

目的探讨Fas／FasL（Fas配体）在原发性肝细胞肝癌（HCC）组织中的表达及其与乙肝病毒（HBV）感染的关系。方法用免疫组化S-P法检测21例肝癌组织及其10例癌旁组织Fas／FasL的表达。结果在肝癌和癌旁组织中Fas表达的阳性率分别为52．38％和80．00％（P〈0．05）,FasL分别为66．67％和40．00％（P〈0．05）。在HBsAg阳性和阴性组Fas表达的阳性率分别为50．00％和66．67％（P〉0．05）;FasL分别为61．11％和100％（P〈0．05）。肝癌组织中Fas、FasL表达与性别、年龄、肿瘤大小无关,与癌栓转移呈负相关,FasL与分化程度有关。结论肝癌细胞能下调Fas及上调FasL的表达而使凋亡受阻,HBV感染能抑制肝癌组织FasL的表达,可能是HBV在HCC的发牛及发展讨稃中的致痛机制。     

Correlation between Fas and FasL proteins expression in normal gastric mucosa and gastric cancer

The study's objective was to assess the expressions of Fas and FasL proteins in gastric cancer in correlation with chosen clinicohistological parameters. Fas and FasL expression was analyzed in 68 patients with gastric cancer, using the immunohistochemical method. The expression of Fas was found to be lower in gastric cancer cells than in healthy mucosa, both in the lining epithelium and in glandular tubes (28% vs. 48% and 44%; p < 0.001). The expression of FasL was also markedly lower in cancer cells than in glandular tubes, yet higher than in the lining epithelium (51% vs. 73% and 14%; p < 0.01). Positive expressions of FasL and Fas were lower in less advanced gastric cancer cells (T1, T2), than in more advanced tumors (T3, T4), but only in the case of FasL was this difference statistically significant (p < 0.05). Our findings seem to confirm the theory of the impact of apoptotic disorders at the level of Fas receptor and FasL protein in the process of gastric cancer formation and growth, which is manifested in the varied expressions of these proteins in gastric cancer and in the normal lining and glandular epithelium of the stomach. However, the lack of significant differences in the expressions of Fas and FasL in correlation to other clinicohistological parameters indicates the existence of mechanisms that have a greater impact on the process of differentiation of gastric cancers. This in our opinion eliminates these proteins as prognostic factors.     

二氮嗪对长时程低温保存大鼠心脏Fas/FasL蛋白表达的影响

本文旨在研究线粒体ATP敏感性钾(mitochondrial ATP-sensitive potassium channel,mitoKATP)通道开放剂二氮嗪(diazoxide,DE)对离体长时程低温保存的大鼠心脏促凋亡蛋白Fas和FasL表达的影响.利用Langendorff离体大鼠心脏灌注法,观察心脏在4 oC含或不含(对照组)DE的Celsior保存液保存8 h后,复灌期心脏作功量(rate-pressure product,RPP)变化情况,采用原位末端标记(TdT-mediated dUTP nick end labeling,TUNEL)染色法检测心肌细胞凋亡和免疫组织化学方法检测Fas和FasL蛋白表达情况.结果显示,在Celsior保存液中加入DE(30 pmol/L),复灌期RPP的恢复率在多个复灌时间点上优于对照组;同时可降低长时程低温保存心脏心肌细胞凋亡指数,减少Fas和FasL蛋白的表达.DE的上述作用可被mitoKAxr通道特异性阻断剂5.羟基葵酸盐(5-hydroxydecanoate,5-HD)所取消.以上结果提示,DE可能通过激活mitoKATP通道来减少Fas和FasL蛋白表达,从而减轻大鼠心肌缺血/再灌注损伤后的心肌细胞凋亡.     

Puerarin decreases apoptosis of retinal pigment epithelial cells in diabetic rats by reducing peroxynitrite level and iNOS expression

The purpose of this study was to investigate the protective effect of puerarin on retina pigment epithelial (RPE) cells of diabetic rats against apoptosis. One hundred and eight Sprague-Dawley (SD) rats were randomly divided into 3 groups: control group, streptozotocin (STZ) group and puerarin group. STZ and puerarin groups received 3 d of STZ injection (45 mg/kg per day, i.p.). Additionally, puerarin groups were treated with puerarin (140 mg/kg, i.p.) from the 4th day to the end of experiment. The rats from different groups were sacrificed on 20, 40 and 60 d after STZ injection for harvesting RPE cells. Western blot analysis, DNA laddering, RT-PCR and immunohistochemistry were used for determining the expression of nitrotyrosine (NT, the foot print of peroxynitrite), cell apoptosis, iNOS mRNA and Fas/Fas ligand (FasL) signal transduction in RPE cells, respectively. The results showed that control group maintained low apoptosis level and little NT, iNOS mRNA, Fas/FasL protein expressions, as well as normal blood glucose and body weight during 60 d of the experiment. Compared with control group, STZ group showed obvious apoptosis and higher NT, iNOS mRNA, Fas/FasL protein expressions from 20 d after STZ injection. Puerarin relieved apoptosis of RPE cells and decreased NT, iNOS mRNA, Fas/FasL protein expressions in puerarin group 20 or 40 d after STZ injection, compared with STZ group. These results suggest puerarin can decrease RPE cells apoptosis in diabetic rats by reducing peroxynitrite level and iNOS expression, thus being a potential therapeutic agent in controlling of diabetic retinopathy.     

Evaluation of the Fas/FasL signaling pathway in diabetic rat testis

We investigated the role of the Fas/Fas ligand (FasL) signaling pathway in diabetic male infertility. Male rats were divided into two groups: a control group and a streptozotocin induced diabetic group. Thirty days after induction of diabetes, samples of testes were harvested and fixed in 10% formalin for light microscopy. Germ cell apoptosis was determined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) and immunostaining of caspase 8 and active caspase 3. We also investigated the expressions of Fas and FasL using immunohistochemistry. Streptozotocin-induced diabetes caused severe histopathological damage and increased apoptotic tubule and apoptotic cell indices, caspase 8 and caspase 3 expressions, and Fas and FasL-immunopositive cells in the rat testes. We suggest that the Fas/FasL signaling pathway may play a role in male infertility caused by diabetes.     

Effect of simvastatin on endothelial cell apoptosis mediated by Fas and TNF-α

Although there is evidence suggesting that statins may exert an endothelial protecting effect, recent in vitro data have shown that these compounds may induce endothelial cells (EC) apoptosis. We previously reported that the Fas-death receptor may induce apoptosis of the liver sinusoid endothelial cells (LSEC), and that TNF-α increases the susceptibility of these cells to suffer Fas-mediated apoptosis. Based on this evidence, in this study, we investigated the effect of simvastatin on Fas-mediated LSEC apoptosis. Simvastatin induced a significant reduction in LSEC viability, in a dose dependent manner, under serum-containing or serum-free conditions. This effect was prevented by mevalonate and GGPP, indicating the role of hydroxy-3-methylglutaryl-CoA reductase. The simvastatin effect on LSEC death was not associated with increased activation of caspase-3. We found that simvastatin increased the susceptibility of LSEC death mediated by Fas. Further, simvastatin increased LSEC-apoptosis induced by Fas and TNF-α. Mevalonate and GGPP partially prevented simvastatin-induced sensitization to LSEC death mediated by Jo2 and TNF-α, but not Jo2 alone. Simvastatin did not induce up-regulation of the Fas on the LSEC. Our results provide evidence of simvastatin in modulating Fas-mediated apoptosis in endothelial cells. These results may have clinical implications in those clinical conditions associated with high levels of FasL and TNF-α.     

淋巴结内FasL蛋白及其mRNA的表达

ＦａｓＬｉｇａｎｄ（ＦａｓＬ）与Ｆａｓ结合诱导细胞凋亡。这一机制对机体免疫反应可能起调节作用。运用ＦａｓＬ多克隆抗体、人工合成ＦａｓＬ寡核苷酸探针分别对淋巴结内ＦａｓＬ蛋白及ｍＲＮＡ进行免疫组织化学检测和原位杂交。结果：正常大鼠淋巴结副皮质区散在分布ＦａｓＬ阳性细胞;非特异性反应性增生的淋巴结内有大量ＦａｓＬ阳性细胞,主要分布在副皮质区,同时输出淋巴管内可见ＦａｓＬ阳性细胞。这为Ｆａｓ系统在参与淋巴细胞凋亡,以维持机体免疫平衡方面的作用提供了证据,同时也提示Ｆａｓ系统可能与某些感染性疾病的发病有关。     

Is extravasation a Fas-regulated process?

The monolayer of endothelial cells that coats the luminal surface of the vessel wall has numerous physiological functions, including the prevention of coagulation, control of vascular permeability, maintenance of vascular tone and regulation of leukocyte extravasation. Recently, we detected functional Fas ligand (FasL) expression on the endothelial lining of blood vessels. FasL induces apoptotic cell death in the multitude of cell types that express its receptor, Fas. Here, we review the function of vascular endothelium in controlling leukocyte extravasation, and illustrate how the regulation of endothelial FasL expression might contribute to this process. We also describe the role of leukocyte extravasation in angiogenesis and atherosclerosis, and we suggest that FasL gene transfer might provide a means of treating diseases of the proliferative vessel wall, particularly those that result from the detrimental infiltration of inflammatory cells.     

Camptothecin induces the transit of FasL trimers to the cell surface in apoptotic HEp-2 cells

Fas ligand (L) is a membrane protein from the tumor necrosis factor (TNF) family. It induces apoptosis upon contact with its Fas/CD95/APO1 receptor. Trimerization of FasL on the surface of effector cells is essential in the binding of the Fas trimer of the target cells. The receptor then recruits an adaptor and caspase-like proteins which lead apoptosis. This paper reports on the fate of FasL in HEp-2 cells committed to apoptosis by induction with campthotecin. Our main results demonstrated that in non-apoptotic cells, FasL aggregates in the cytoplasm forming trimers of 120 kDa. Apoptosis increases the trimeric FasL species, but also induces its dissociation into monomers of 35 kDa. In conclusion, camptothecin appears to perturb the Fas and FasL segregation in the cytoplasm by promoting the transit of FasL to the cell surface, thus fostering a process of autocrine or paracrine apoptosis. FasL is trimerized prior to Fas/FasL complex formation, and after apoptosis, FasL undergoes an intense turnover.